In previous work I have demonstrated that RF mice inherit genes that code for two discrete effects on endogenous MuLV metabolism and leukemogenesis. One is a single gene, closely linked to the Fv-1 locus, that coordinately restricts xenotropic virus expression at 6 months of age and subsequent spontaneous leukemogenesis. This gene is dominant in the AKR x RF F1 hybrid mouse, and its restriction is reversed by treatment of both RF and AKR x RF F1 mice with 3-methylcholanthrene. This gene may be the Fv-1 gene itself. The second genetic effect results in low ecotropic virus titers and complete absence of xenotropic virus expression in RF mice. These phenotypes are recessive in the AKR x RF F1 mouse, and are unaffected by 3-methylcholanthrene treatment. The aim of the experiments proposed in this application is to probe the mechanisms of action of these mouse genes. The techniques to be employed include genetic crosses, assays for endogenous MuLV expression in mice (the UV-XC plaque assay for ecotropic virus, and a fluorescent focus assay for xenotropic virus), subcutaneous thymus grafting, in vitro and in vivo infection of mouse cells with MuLV, and renaturation kinetics of radioactively labeled viral cDNA in the presence of excess leukemic cell DNA. The proposed studies will investigate the interrelationships of mouse cellular genes, endogenous type-C viruses, and chemical carcinogens in the process of leukemogenesis.